Showing papers in "Anesthesiology in 1981"

Neural Blockade: In Clinical Anesthesia and Management of Pain

Abstract: (Section Titles) Introduction Pharmacology and Physiology of Neural Blockade Techniques of Neural Blockade Neural Blockade in the Management of Pai

Studies in the Primate on the Analgetic Effects Associated with Intrathecal Actions of Opiates,α-Adrenergic Agonists and Baclofen

Abstract: The effects of intrathecally administered opiates (morphine sulfate and meperidine), α-adrenergic agonists (clonidine and ST-91) and baclofen were examined on the shock titration thesh-old of macaque monkeys chronically prepared with intrathecal (I) or epidural (E) catheters. Spinal opiates produced

Anesthetic Doses Blocking Adrenergic (Stress) and Cardiovascular Responses to Incision—MAC BAR

Abstract: The reaction to stress, while vital to the conscious animal, may be detrimental to the surgical patient. To assess the stress-ablating action of different anesthetics (halothane, enflurane, morphine, and spinal) and anesthetic doses, we studied the responses in plasma norepinephrine, muscle movement, pupil diameter, heart rate, and blood pressure to induction of anesthesia and incision in 170 unpremedicated healthy adults. The age-adjusted dose (mean +/- SD) of anesthesia that blocked the adrenergic response in 50 per cent of individuals who had a skin incision (MAC BAR) was 1.45 +/- 0.08 MAC for halothane, 1.60 +/- 0.13 MAC for enflurane, or 1.13 +/- 0.09 +/- mg/kg for morphine sulfate (each anesthetic was given with 60 per cent nitrous oxide). No patient with a level of spinal anesthesia that blocked the pain of incision had an adrenergic response to incision. Increasing doses of halothane and morphine were associated with less of a cardiovascular response to incision (as measured by rate-pressure product); this was not true for enflurane. No patient with an adequate level of spinal anesthesia had a cardiovascular response to skin incision. The changes in heart rate, blood pressure, rate-pressure product, and plasma norepinephrine content that occurred with induction of anesthesia tended to equalize these values between patients, regardless of anesthetic dose, and for all individual and combined anesthetics. That is, if a patient's heart rate while awake was below 63 beats/min, heart rate tended to rise 58 per cent of the difference between heart rate while awake and 63 beats/min, and vice versa. Similarly, the change in blood pressure with induction averaged 75 per cent of the difference between systolic blood pressure while awake and 88 torr. The average for the change in rate-pressure product with induction was 79 per cent of the difference between rate-pressure product while awake and 5917 torr.beats/min. It was concluded that all the anesthetics tested can prevent the neuroendocrine response to skin incision at clinically attainable doses. Thus, comparisons of neuroendocrine stress during surgery require quantitation of anesthetic dose. If adverse effects of surgery are related to the neuroendocrine stress that surgical manipulations induce, the hypothesis "the less anesthetic the better" may be wrong.

Anticoagulation Following Placement of Epidural and Subarachnoid Catheters: An Evaluation of Neurologic Sequelae

Abstract: The incidence of neurologic complications arising from anticoagulant therapy, following epidural and subarachnoid catheterization in 3,164 and 847 patients, respectively, was determined. Twenty patients experienced minor neurologic complications or low back pain which was self-limiting and resolved with time. There was no incidence of peridural hematoma leading to spinal cord compression. This investigation shows that the occurrence of symptomatic hematomas following anticoagulation in patients with epidural or subarachnoid catheters is a very rare complication, assuming proper patient selection, an atraumatic technique, and appropriate monitoring of anticoagulant activity.

Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers.

Abstract: Sevoflurane was submitted to phase-1 studies in man following extensive testing in animal species without evidence of toxicity. Sevoflurane, 2–3 per cent inspired during maintenance, was administered with oxygen to produce one hour of anesthesia in six healthy adult male volunteers. Respiratory and cardiovascular functions, the electroencephalogram, arterial blood gases, blood sevoflurane, inorganic fluoride and total, nonvolatile fluorine concentrations, and inspired and mixed expired sevoflurane concentrations were measured during exposure. Concentrations of expired sevoflurane, blood and urinary fluoride, and total nonvolatile fluorine metabolites were also measured after anesthesia. During exposure spontaneous respiratory frequency increased 28 per cent, respiratory minute volume changed insignificantly, and Paco2s averaged 50 torr. Pao2s remained near 400 torr. Arterial systolic blood pressure declined an average of 17 per cent. Pulse rate changed insignificantly. After an hour of exposure arterial blood serum inorganic fluoride concentrations averaged 22 μM and plasma nonvolatile organic fluorine concentrations averaged 9.1 mg/l, or 61.3 μM. Uptakes of sevoflurane averaged 94 (±63 SD) mmol. Following exposure 37 (±12) mmol of unaltered sevoflurane were estimated to be excreted in exhaled air and 0.90 mmol of inorganic fluoride and 163 mg, or 1.43 (±0.26) mmol of organic fluorine were excreted in the urine. Recoveries in exhaled air and urine averaged 51.5 (±2.4) per cent of uptake. There was no significant drug-exposure-related change in the chest radiogram, electrocardiogram, electroencephalogram, urinalysis results, complete blood count, prothrombin time, serum electrolytes, transaminases, or hepatic and renal functions during four weeks following exposure compared with preexposure values. Sevoflurane produced anesthesia of excellent quality; it appears to undergo limited biotransformation and to have little or no systemic toxicity.

Nutrition for the patient with respiratory failure: glucose vs. fat.

Abstract: High glucose intakes given during administration of total parenteral nutrition (TPN) have been demonstrated to increase CO2 production. The workload imposed by the high CO2 production may precipitate respiratory distress in patients with compromised pulmonary function. Changes in CO2 production and O2 consumption induced by TPN using either glucose as the entire source of non-protein calories, or fat emulsions as 50 per cent of the non-protein calories, have been analyzed either in patients with chronic nutritional depletion or in acutely ill patients secondary to injury and infection. In patients with chronic nutritional depletion, shifting from the lipid to the glucose system caused a 20 per cent (P less than 0.025) increase in CO2 production which resulted in a 26 per cent increase in minute ventilation (P less than 0.01). In the acutely ill patients receiving the glucose system, CO2 production was significantly higher than in those receiving the lipid system (179 vs. 147 ml.min-1.m-2; P less than 0.01. Fat emulsions can serve as a source of non-protein calories and are associated with lesser degrees of CO2 production than isocaloric amounts of glucose.

Effects of high-dose fentanyl anesthesia on the electroencephalogram.

Abstract: The purpose of this study was to define the EEG changes produced in humans by fentanyl 30-70 microgram/kg during cardiac surgery. The authors have also assessed awareness in the patients. Thirty-nine patients were studied; oral lorazepam or intramuscular morphine was used as premedication. Anesthesia was induced with intravenous injection of fentanyl over 2 min and the patients were ventilated with either air/O2 (24 patients) or N2O/O2 (15 patients). The EEGs recorded until the start of cardiopulmonary bypass were visually analyzed, classified into EEG stage, and plotted graphically as narcograms. Computerized 3-dimensional power spectral analysis and wide band spectral analysis were carried out on representative EEGs. The EEG effects of fentanyl are consistent and are characterized by high-voltage slow delta waves. Nitrous oxide had no effect on the EEG responses to fentanyl. Computer analysis confirmed the visual interpretation. There was no incidence of awareness. The authors conclude from this study that fentanyl after premedication is a suitable drug for providing unconsciousness, analgesia, and amnesia during cardiac surgery.

Inhibition of cerebral oxygen and glucose consumption in the dog by hypothermia, pentobarbital, and lidocaine.

Abstract: The effect of lidocaine, 160 mg/kg, and pentobarbital, 40 mg/kg, on cerebral oxygen and glucose consumption was examined at brain temperatures of 37 degrees C, 28 degrees C, and 18 degrees C. Cerebral metabolic rate was measured in dogs on cardiopulmonary bypass circulation by using the sagittal sinus outflow technique. When studied separately, both drugs suppressed synaptic transmission and inhibited metabolism, and a maximum effect was obtained when the EEG became flat. Using halothane 1-1.5 per cent as the control condition, this function-metabolism coupled inhibition was about 30 per cent. When the drugs were studied in combination, it was found that when lidocaine was given after pentobarbital, it caused an additional metabolic inhibition of 15-20 per cent, while pentobarbital given after lidocaine had no effect. It is concluded that pentobarbital has no inhibitory effect on cerebral metabolism in the absence of synaptic activity, while lidocaine--in addition to the effect related to suppression of synaptic transmission--has a specific "membrane stabilizing" effect. In analogy to its local anesthetic action, lidocaine blocks the Na+ channels and restricts the Na+-K+ leak fluxes. The load on the ion pump is reduced and metabolism is decreased accordingly. This specific effect on lidocaine was evident also at brain temperatures of 28 degrees C and 18 degrees C. The study supports the possibility that lidocaine, like hypothermia, may provide protection for the ischemic brain.

Time course and mechanisms of lung-volume increase with PEEP in acute pulmonary failure.

Abstract: To determine the effects of a step change in end-expiratory pressure on functional residual capacity (FRC) and lung-thorax compliance (CLT), 10 cm H2O positive end-expiratory pressure (PEEP) was applied in eight patients who needed mechanical ventilation for acute pulmonary failure. Of the total change in FRC, 66 +/- 5.3 per cent (mean +/- SEM) was complete within the next breath, and 90 per cent change was achieved in 4.6 +/- 1.4 breaths (24 +/- 6.4 sec). There was no statistically significant difference between times to 90 per cent FRC change with application and with removal of PEEP. In another 13 patients, PEEP was increased in 5 cm H2O steps from 3 to 18 cm H2O. Mean FRC at 3 cm H2O PEEP was 1.51 +/- 0.20 1 (55 +/- 7.0 per cent predicted supine value). Mean CLT did not change significantly until 18 cm H2O PEEP was reached, at which point it decreased (P < 0.005). The static compliance derived from change in FRC (deltaFRC/deltaPEEP) increased with increments of PEEP (P < 0.05) compared with the initial level. At PEEP levels of 8 and 13 cm H2O, mean FRC was larger than would be predicted from mean CLT (P < 0.005), but it was not significantly different at 3 cm H2O PEEP. The lung component accounted for 62 +/- 3.7 per cent of the lung-thorax compliance difference. These data define a time-dependent increase in lung volume that resembles pressure-volume hysteresis in normal man. Possible mechanisms include surface tension changes, recruitment of nonventilated lung, and stress relaxation of lung and chest wall. This study may explain the greater efficiency of PEEP compared with large tidal-volume ventilation in increasing PaO2 in patients with acute pulmonary failure.

Halothane Depression of Myocardial Slow Action Potentials

Abstract: Effects of halothane on myocardial electrophysiologic and contractile properties were studied by simultaneous measurement of action potentials (APs) and contractions in guinea pig papillary muscle. Muscles were stimulated by field electrodes and normal responses measured before, during, and after recovery from halothane application. Halothane was administered in 0.5 per cent to 4 per cent concentrations in 5 per cent CO2–95 per cent O2 bubbled through standard Tyrode perfusing solutions. Slow action potentials were then induced with 10−7 isoproterenol in partially depolarized muscles (typically −40 mV in 26 mM K+ media). AP characteristics and accompanying contractions were again measured before, during, and after halothane application. The maximum rate of rise (+&OV0312;max) of the normal (fast) AP was not depressed in any concentration of halothane, although amplitude and duration were decreased in 3 per cent halothane. In contrast, halothane depressed +&OV0312;max of the slow AP to 61 per cent, 28 per cent, and 14 per cent of control, in concentrations of 1, 2 and 3%, respectively. Decreased duration and decreased amplitude (85% of control of the slow AP), or loss of excitability (4 of 7 muscles) occurred in 3 per cent halothane. Initially, halothane application caused a 5 per cent enhancement of tension with both fast and slow APs. In 0.5 per cent halothane, contractions subsequently declined to steady-state levels of 66 per cent (fast AP) and 76 per cent (slow AP) of control. Contractions were depressed linearly with log dose to 18 per cent (fast AP) and 5 per cent (slow AP) of control in 3 per cent halothane. Halothane concentrations of 1 per cent and greater inhibit slow (Na+ – Ca++) channels which mediate the slow action potentials. The negative inotropic effect of halothane may be due in part to decreased Ca++ influx through the slow channel. The negative inotropic effect of 0.5 per cent halothane, in which the slow AP is unaffected, suggests that additional mechanisms, not involving the slow channel, also participate in the negative inotropic action of halothane.

Clinical Pharmacology of ORG NC45 (NorcuronTM): A New Nondepolarizing Muscle Relaxant

Abstract: To determine the neuromuscular effects of a new muscle relaxant, ORG NC45 (Norcuron), a monoquaternary homologue of pancuronium, 84 ASA Class I or II patients were studied under halothane and nitrous oxide anesthesia. The ED50 (dose of muscle relaxant causing a 50% depression of twitch tension) of pancuronium and ORG NC45 was 0.022 mg/kg (r = 0.90) and 0.015 mg/kg (r =0.80), respectively, for a potency ratio of 1.5 (0.022/0.015). The duration of action (time from injection to 90% recovery of control twitch tension) was 27 +/- 5 min with ORG NC45, 0.02 mg/kg, and 65 +/- 16 min with pancuronium in an equivalent dose of 0.03 mg/kg. The increase in duration of neuromuscular blockade from repetitive doses was greater with pancuronium than with ORG NC45. Reversal of an ORG NC45 neuromuscular blockade was accomplished with doses of neostigmine slightly less than those required for pancuronium. Under thiopental-nitrous oxide anesthesia, endotracheal intubation was easily performed using ORG NC45, 0.07-0.14 mg/kg. The duration of action of ORG NC45, 0.07 mg/kg, was about one-third that of pancuronium (0.1 mg/kg). It was concluded that ORG NC45 is more potent and has a shorter duration of action with both initial and repetitive doses than does pancuronium. With these characteristics and the reported lack of cardiovascular effects, the authors believe further clinical trials are warranted.

Isoflurane and Cerebrospinal Fluid Pressure in Neurosurgical Patients

Abstract: The effect of isoflurane on cerebrospinal fluid pressure (CSFP) was determined in 20 patients undergoing craniotomy for intracranial supratentorial neoplasm or hepatoma. In 15 of these patients, following endotracheal intubation, hyperventilation sufficient to result in PaCO2 25-30 torr was begun simultaneously with the introduction of 1 per cent isoflurane. In the remaining five patients ventilation was equivalent, but normocapnia was maintained by adding CO2 to the inspired gases. In the hypocapnic patients CSFPs did not increase above awake values (range 5-45 torr) following isoflurane administration. In the normocapnic patients (CSFPs consistently increased. In three of these five patients the increases were precipitous, but were corrected rapidly by establishment of hypocapnia. The authors conclude that the known cerebral vasodilator properties of isoflurance can be countered effectively by hypocapnia. Furthermore, unlike the situation with halothane, it is not necessary to establish hypocapnia prior to introducing isoflurane in order to avoid CSFP increases.

Hemodynamic Changes during Fentanyl—Oxygen Anesthesia for Aortocoronary Bypass Operation

Abstract: Fentanyl in doses of 50-60 microgram/kg has been reported to produce anesthesia with remarkable hemodynamic stability in patients with coronary artery disease (CAD). Because the authors had observed hypertension and tachycardia in response to noxious stimulation during aortocoronary bypass (ACB) operations in patients so anesthetized, they studied the hemodynamic changes and anesthetic conditions produced by fentanyl/O2/relaxant anesthesia in patients undergoing elective ACB. Twelve patients with left ventricular (LV) ejection fractions greater than 0.4 were maintained on propranolol until 10 hours before operation and were premedicated with fentanyl, diazepam, and scopolamine. Cannulae were inserted before the study commenced for measurement of intravascular pressures, arterial blood gases, and thermodilution cardiac output. The patients breathed 100 per cent oxygen throughout the study. Controlled ventilation aided by succinylcholine to reduce truncal rigidity maintained PaCO2 at 30-45 torr. Measurements were made after each of the following: breathing oxygen (control), 10 microgram/kg fentanyl, 50 microgram/kg fentanyl, and 0.1 mg/kg pancuronium, tracheal intubation, skin incision, and sternotomy. Fentanyl alone produced no significant hemodynamic changes. Fentanyl and pancuronium in combination produced increased heart rate and reduced stroke volume. Significant and progressively greater increases in mean arterial pressure and systemic vascular resistance followed intubation, skin incision, and sternotomy. Chest rigidity occurred in every patient at a lower fentanyl dose than did unresponsiveness. While fentanyl, 62.4 +/- 2.9 microgram/kg (SE), produced minor hemodynamic changes, it failed to block hemodynamic responses to noxious stimulation. Such changes resulted in increased cardiac work, and could have affected myocardial oxygen balance unfavorably. In eight of the 12 patients, following the last set of measurements, supplementary anesthetic agents were required to maintain hemodynamic stability during the surgical procedure. The authors suggest that this fentanyl/O2/relaxant technique should be modified for patients with severe CAD and reasonably good LV function.

The use of H1 and H2 histamine antagonists with morphine anesthesia: a double-blind study.

Abstract: High doses of morphine can produce significant cardiovascular effects generally attributed to histamine release. The authors examined the possibility that H1 and H2 histamine antagonists might prove beneficial in preventing these responses. In a randomized double-blind study, four groups of 10 patients each received 1 mg/kg morphine and either a placebo, diphenhydramine (H1), cimetidine (H2), or both of the histamine antagonists. The morphine-placebo group demonstrated a marked elevation in plasma histamine levels (880 +/- 163 to 7437 +/- 2684 pg/ml), a decrease in systemic vascular resistance (SVR) (15.5 to 9.0 l torr/(l . min-1) and diastolic BP (71 +/- 3 to 45 +/- 4 torr) and an increase in cardiac index (CI) (2.4 +/- 0.2 to 3.0 +/- 0.21 . min-1 . m-2). The administration of either cimetidine or diphenhydramine with morphine provided minimal protection. Those patients who received morphine and both antagonists demonstrated significant attenuation of these responses (CI 2.5 +/- 0.2 to 2.5 +/- 0.1 l . min-1 . m-2; SVR 17.4 to 14.6 torr/(l . min-1) although plasma histamine levels showed a comparable increase (1059 +/- 222 to 7653 +/- 4242 pg/ml). These data demonstrate directly that many of the hemodynamic effects of morphine can be attributed to histamine release. They further demonstrate that significant hemodynamic protection can be obtained by the use of histamine antagonists and the combination of H1 and H2 antagonists is superior to either given alone.

Intrathecal Injection of Morphine for Obstetric Analgesia

Abstract: Intrathecal injection of morphine was used to provide obstetric analgesia in 20 primiparous women in labor. When the cervix was at least 3 cm dilated, morphine, 1 or 2 mg, was injected intrathecally. In all parturients, labor pains were completely relieved after 15-60 min and analgesia lasted as long as eight to 11 hours. The analgesia was not associated with any alteration of pin-prick sensation or motor power, and there was no change in the arterial blood pressure or heart rate. All infants were delivered vaginally by use of episiotomy annd a low forceps, except two infants of mothers in the 2 mg of morphine group who needed cesarean section. During the second stage of labor, analgesia was supplemented by lidocaine, 2 per cent, using local perineal infiltration in 14 parturients and pudendal block in two parturients, and by epidural block in four parturients. Nineteen of the 20 newborns cried immediately at birth, and had Apgar scores o 7-9 at 1 min and 8-10 at 5 min. During the first 24 hours of life, the neurobehavioral responses of all newborns were scored as normal. Systemic maternal side effects such as somnolence, nausea, vomiting, and itching occurred in a high proportion of the parturients. However, in the majority of cases, these side effects were mild. Only two parturients of the 2 mg morphine group complained of marked somnolence, itching, and vomiting, which persisted post partum; these were effectively reversed by the specific antagonist naloxone. The analgesic effect of intrathecal morphine can be attributed to its action on the opiate receptors in the substantia gelatinosa of the dorsal horn of the spinal cord. However, supraspinal effects of morphine cannot be excluded. The low lipid solubility of morphine can explain its slow onset and prolonged duration of action. Also, this will result in minimal systemic absorption of morphine, which protects the fetus and results in selective maternal analgesia.

Tissue redistribution of fentanyl and termination of its effects in rats

Abstract: The kinetics of fentanyl elimination from plasma suggest its rapid and extensive uptake by tissues. The authors determined the relationships between tissue and plasma concentrations of fentanyl. Six rats injected iv with 3H-fentanyl citrate (50 micrograms/kg) were sacrificed at each of the following times: 1.5, 5, 15, 30, 60, 120, and 240 min after injection. Tissues were analyzed for unchanged 3H-fentanyl citrate and for total 3H-radioactivity. Fentanyl effects were evident 10 s after injection; recovery began at 5 min and was complete within 60 min. Fentanyl concentrations in brain, heart, and lung equilibrated with that in plasma before 1.5 min and declined at the same rate (t 1/2 alpha = 8 min, t 1/2 beta = 45 min). Fentanyl uptake by muscle and fat was slower and equilibration with plasma occurred by 120 min. Muscle accumulated 56 per cent of the dose within 5 min by which time brain fentanyl levels had declined by 90 per cent. Only 6 per cent of the dose was in fat at 5 min but this increased to a maximum of 17 per cent at 30 min. Fentanyl was extensively metabolized; metabolites represented 25 per cent of body 3H-radioactivity at 15 min, and 80 per cent at 4 h. The authors conclude that the short duration of fentanyl effect is due to its rapid redistribution from sites of action in the brain to sites of storage (muscle and fat) and biotransformation (liver). The elimination of fentanyl from the body is governed by its reuptake from storage sites and its metabolism in the liver. Most of the dose is ultimately excreted in the form of fentanyl metabolites in urine.

Effect of Spinal Anesthesia on Adrenergic Tone and the Neuroendocrine Responses to Surgical Stress in Humans

Abstract: In order to quantitate the effect of spinal anesthesia on adrenergic tone, plasma levels of norepinephrine (NE) and epincphrine (EPI) were measured by radioenzymatic assay in 24 patients prior to elective lower body surgical procedures. The subsequent neuroendocrine responses to surgical stress of 16 of these patients were then compared to those of 10 patients receiving inhalation anesthesia (halothane-nitrous oxide). High thoracic dermatome spinal anesthesia caused suppression of both arterial plasma NE and EPI and a fall of mean arterial pressure (MAP); in contrast, no changes of NE, EPI, or MAP were observed in patients receiving low spinal anesthesia. Overall, there was a relationship between the sensory dermatome anesthesia level and changes of both plasma NE (r = 0.71, P < 0.001) and EPI (r = 0.52, P < 0.02). In the inhalation anesthesia group, plasma NE increased during the operation and plasma levels of NE, EPI, growth hormone, and cortisol were elevated during the postoperative recovery period. These neuroendocrine responses to surgical stress were not observed in patients receiving either low or high spinal anesthesia. Thus, the effect of spinal anesthesia on adrenergic tone depends on the cord level of anesthesia and can be quantitated by measurement of plasma catecholamines. The neuroendocrine responses to surgical stress were prevented in patients who received low spinal anesthesia and who had no suppression of efferent adrenergic tone. These findings indicate that neural afferents from the site of tissue injury, which were blocked by low spinal anesthesia, mediated both the adrenergic and the hormonal responses to surgical stress in the inhalation anesthesia group.

Are the Myocardial Functional and Metabolic Effects of Isoflurane Really Different from Those of Halothane and Enflurane

Abstract: The effects of low (1.6 per cent end-tidal) and high (3.2 per cent end-tidal) concentrations of isoflurane were compared in a closed-chest dog preparation. Hemodynamics were evaluated using cardiac catheterization for measuring mean right atrial (RAP) and aortic (MAP) pressures; left ventricular end-diastolic (LVED) and peak systolic (LVSP) pressures and maximum rate of pressure rise (LVdP/dt); and the cardiac output (CO) by the dye dilution technique. Myocardial blood flow (MBF) and metabolism were estimated by 133Xe washout from the great cardiac vein and measurement of oxygen and various substrates in aortic and coronary venous blood. Ventricular functional responses to altering preload (LVEDP) by blood infusion or withdrawal, and afterload (systemic vascular resistance, SVR) by balloon occlusion of the aorta were measured at low and high isoflurane concentrations. Body temperature, Pao2 and Pao2 were maintained constant. High concentrations of isoflurane (as compared to low concentrations) produced 40–60 per cent decreases in MAP, CO, LVSV, LVdP/dt, and SVR without changing heart rate or LVEDP. MBF and myocardial O2 uptake were decreased to the same extent without change in O2 or lactate extraction by the heart. Increased preload resulted in small increases in cardiac output at low LVEDP (13–15 torr), but little or no change at higher values (18–23 torr) during both high and low isoflurane concentrations. Likewise, increased afterload decreased ventricular function at both concentrations of isoflurane. When the effects of halothane and enflurane were compared in identical, acute and chronic preparations, the results were similar except the filling pressures (LVEDP) were significantly increased by high concentrations (more than two times MAC) of the other two anesthetics. In addition, there was no change in systemic vascular resistance produced by halothane or enflurane. Thus, although isoflurane produces a dose-related depression of ventricular function in the intact dog, the degree appears to be somewhat less than that seen with halothane and enflurane. This difference may be related to the decreased afterload resulting from the administration of isoflurane and perhaps a minor degree of cardiac sympathetic stimulation. Myocardial perfusion was decreased to the same degree as function and oxygenation was well maintained.

Increase in extracellular potassium in the brain during circulatory arrest: effects of hypothermia, lidocaine, and thiopental.

Abstract: The effect of temperature (37 degrees C, 28 degrees C, and 18 degrees C), 160 mg/kg lidocaine, and 40 mg/kg thiopental on the efflux of cellular potassium in the cerebral cortex during complete global ischemia was examined. Cerebral ischemia was induced in dogs on cardiopulmonary bypass circulation by stopping the pump. Potassium concentration was measured on the brain surface by a valino-mycine-membrane electrode, which in its response corresponded well to an inserted microelectrode. Hypothermia reduced the ischemic potassium efflux rate to about 50 per cent at 28 degrees C, and about 25 per cent at 18 degrees C. At all temperature levels lidocaine caused an additional reduction in the potassium efflux rate of about 50 per cent, probably by reducing membrane ion permeability in accordance with its local anesthetic action. Thiopental had no effect on the potassium efflux during ischemia. This study opens the possibility that lidocaine, like hypothermia, may provide protection of the ischemic brain.

Role of Histamine in the Hypotensive Action of d-Tubocurarine in Humans

Abstract: The administration of d-tubocurarine (dTc) to animals and humans has been reported to produce hypotension. Experiments in animals suggest that the hypotension is a result of both ganglionic blockade and histamine release. In order to determine the role of histamine release in dTc-induced hypotension in humans, the authors developed a sensitive radioenzymatic assay for plasma histamine and measured plasma histamine following dTc administration (0.25-0.75 mg/kg) to 21 surgical patients. While neither fentanyl (3 microgram/kg) nor thiopental (6 mg/kg) produced a significant change in plasma histamine, dTc caused a dose-dependent increase in plasma [dose dTc vs. log (plasma histamine), r = 0.62 P less than 0.003]. The log (plasma histamine) correlated with the dTc-induced hypotension (r= 0.61, P less than 0.005). The data suggest that histamine release is an important factor in the hypotension accompanying dTc administration in humans.

Regional Ischemic Ventricular Dysfunction in Myocardium Supplied by a Narrowed Coronary Artery with Increasing Halothane Concentration in the Dog

Abstract: The effects of increasing inspired halothane concentration (0.5, 1.0, 1.5, 2.0 per cent) upon left ventricular myocardium supplied by a critically narrowed coronary artery and a normal coronary artery were studied in 11 open-chested dogs. Regional ventricular function was measured by continuous recording of ventricular segment length using pairs of implanted miniature ultrasonic length detectors in the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LC) territories before and during critical stenosis of the LAD by a micrometer-controlled snare. Critical narrowing was documented by ischemic regional ventricular function (i.e., post-systolic shortening; systolic lengthening) limited to the LAD territory when FIO2 = 0 for 90 seconds. Hemodynamic variables (aortic, left atrial and left ventricular pressure, and heart rate) were measured, ECG lead II was recorded, and the first derivative of left ventricular pressure (LV dP/dt) and coronary perfusion pressure derived for each halothane concentration before and during LAD narrowing. Increasing halothane was associated with equivalent progressive depression of global ventricular function before and during LAD constriction. Prior to LAD constriction, no ischemic changes in regional function occurred. Regional ventricular function was normal during 0.5 percent halothane in the presence of LAD constriction. With increasing halothane during LAD constriction, ischemic regional ventricular function was observed in the LAD territory in eight of eleven hearts, whereas regional ventricular function remained normal in the LC territory. The epicardial ECG was recorded in three dogs and was insensitive as an indicator of ischemia, becoming abnormal only after severe ischemic changes were established. In these studies, in which heart rate remained constant, arterial blood pressure and LV dP/dt decreased, and left ventricular end-diastolic pressure increased, decrease in blood flow and oxygen delivery due to a lower perfusion pressure distal to the coronary artery narrowing appears to be primarily responsible for the observations. The authors hypothesize that clinically unapparent episodes of regional myocardial ischemia distal to narrowed coronary arteries may be an important cause of perioperative myocardial infarction.